Cell barrier function is, on the one hand, of outmost importance in our lungs, as the respiratory tract is exposed to a hostile environment from both sites: the airways and the vasculature. On the other hand, however, an efficient gas exchange of oxygen (O ₂) and CO ₂ is only possible through a very thin alveolo-capillary membrane. On the vascular site, endothelial cells form a natural barrier, while in the airways epithelial cells are most important for protection of the lung tissues. Moreover, fibroblasts, by transforming to myofibroblasts, are essential for wound closure after mechanical and chemical microinjuries in the respiratory tract. Along this line, loss of cell resistance in vascular endothelial and lung epithelial cells enhances invasion of pathogens (e.g. SARS-CoV-2) and results in pulmonary edema formation, while increasing barrier function of pulmonary (myo)fibroblasts blocks gas exchange in patients with pulmonary fibrosis (PF). Therefore, electrical cell-substrate impedance sensing (ECIS)-based quantification of changes in cell barrier function in lung endothelial and epithelial cells as well as fibroblasts after application of harmful triggers (e.g. hypoxia, receptor agonists and toxicants) is a convenient and state-of-the-art technique. After isolation of primary cells from mouse models and human tissues, changes in cell resistance can be detected in real time. By using lung cells from gene-deficient mouse models, micro (mi) RNAs or the small-interfering (si) RNA technology essential proteins for cell adhesion e.g. ion channels of the transient receptor potential (TRP) family are identified in comparison to wild type control cells. In the future, these proteins may be useful as drug targets for novel therapeutic options in patients with lung edema or pulmonary fibrosis.